Norihisa Takakura

Phase II Study of Docetaxel and S-1 Combination Therapy for Advanced or Recurrent Gastric Cancer

Purpose: To evaluate the efficacy and toxicity of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 for patients with advanced or recurrent gastric cancer. Experimental Design: Patients with advanced or recurrent adenocarcinoma of the stomach and up to one previous chemotherapy regimen were treated with i.v. docetaxel 40 mg/m2 on day 1 and oral S-1 80 mg/m2/d on days 1 to 14 every 3 weeks. Results: Forty-eight patients (median age, 65 years; range, 25-75 years) received a total of 272 treatment cycles (median, 4; range, 1-17). No complete responses and 27 partial responses were observed for an overall response rate of 56.3% [95% confidence interval (95% CI), 38-66%]. Eighteen patients (37.5%) had stable disease and three patients (6.3%) had progressive disease as best response. The tumor control rate (complete response + partial response + stable disease) was 93.8% (95% CI, 83-98%). Median overall survival was 14.3 months (95% CI, 10.7-20.3 months) and median time to tumor progression was 7.3 months (95% CI, 4.3-10.0 months). The most common grade 3 to 4 hematologic toxicities were neutropenia (58.3%), leukopenia (41.7%), febrile neutropenia (8.3%), and anemia (8.3%). The most common grade 3 nonhematologic toxicities included anorexia (14.6%), stomatitis (8.3%), and nausea (6.3%). No grade 4 nonhematologic toxicities were reported and all treatment-related toxicities were resolved. Conclusion: Docetaxel/S-1 combination is highly active and well tolerated in advanced or recurrent gastric cancer. Further investigation in randomized studies is warranted.

The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers

We previously reported that introduction of the wild-typep53 gene into human cancer cells with deletedp53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54∶2287]. This suggests thatp53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer forp53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery.p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutantp53, however, significantly showed fewer apoptotic cells compared with those expressing wild-typep53. Thep53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, where-as mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude thatp53 mutations are associated with the poor response of chemotherapy and radiotherapy.

Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis

Abstract: We report a rare case of hepatic adenomas (HA), in a 20-year-old Japanese girl treated for 6 years with anabolic androgens for aplastic anemia. In a review of the world literature using computer MEDLINE search, we found only 17 cases of androgen-induced HA published between 1975 and 1998 in the English-language literature. The patient was referred to us because of liver lesions detected during a follow-up examination for familial adenomatous polyposis. After being diagnosed with aplastic anemia at 14 years of age, she had been treated with oxymetholone (30 mg/day) for 6 years. Laboratory evaluation revealed normal liver function. Ultrasonography (US) and computed tomography (CT) demonstrated multiple liver lesions. Histopathological examinations of biopsied specimens from the liver tumor showed HA. After the patient was diagnosed with HA, oxymetholone was tapered off. Patients taking androgenic-anabolic steroids should be carefully monitored with US and CT and tumor markers should be measured. This report may be helpful in identifying the population who is at risk of developing hepatic sex hormone-related tumors.

Generalized peritonitis due to spontaneously perforated pyometra presenting as pneumoperitoneum: Report of a case

We report a rare case of generalized peritonitis due to a ruptured pyometra in an 86-year-old woman, and also conduct a review of the previous Japanese literature. The patient presented with muscle guarding and rebound tenderness. Computed tomography (CT) disclosed a cystic mass in the peritoneal cavity, in which an air-fluid level was noted. Pneumoperitoneum around the uterus due to gas production of anaerobic bacteria was noted on a CT. At laparotomy, the uterus was markedly enlarged with a necrotic area on the uterine fundus, which was found to be perforated. A supravaginal hysterectomy and drainage were performed. We found only eight cases of a ruptured pyometra presenting as pneumoperitoneum in the Japanese literature between 1977 and 1999. The most common cause of pneumoperitoneum is a perforation of the gastrointestinal tract. However, other possible causes, as seen in our patient, should also be taken into consideration. Although it is rare, a perforated pyometra should therefore also be considered when elderly women present with acute abdominal pain.

Long-term effects of jejunal pouch added to Roux-en-Y reconstruction after total gastrectomy

Background. Jejunal pouch reconstruction after total gastrectomy has been demonstrated to ameliorate postgastrectomy symptoms, with the process of adaptation taking several months. In contrast to the short-term effects of pouch reconstruction, there are few reports about the long-term consequences (more than 2 years after surgery). Methods. In this study, 22 patients with jejunal pouch (PRY group) and 12 patients without jejunal pouch (RY group) who survived for more than 2 years without any recurrence and were available for follow-up were compared. Patients in the two groups were compared 2 years after surgery in terms of postgastrectomy symptoms, and improvements in body weight and nutritional parameters. Results. Eating capacity at a single meal compared with that in the pre-illness state was significantly better in the PRY group than in the RY group. The total score on the gastrointestinal symptom rating scale (GSRS) in the PRY group was less than that in the RY group (3.17 vs 5.25). The GSRS score for reflux syndrome in the PRY group was significantly better than that in the RY group. Assessment according to Cuschieris gradings revealed that the total score in the PRY group was lower than that in the RY group (2.73 vs 5.92). Among the various symptoms examined, the incidence of dietary restriction and that of heartburn were significantly lower in the PRY group. Conclusion. We conclude that, 2 years after total gastrectomy, the pouch reconstruction had alleviated postgastrectomy symptoms to a greater extent than simple Roux-en-Y reconstruction, but the effectiveness could be improved. The long-term effects of pouch reconstruction should be examined more precisely with an adequate and valid scoring system for determining quality of life.

Rapidly enlarging esophageal duplication cyst

Abstract: We report a rare esophageal duplication cyst, in a 12-year-old girl. The cyst had enlarged rapidly within 2 years. In December 1997, on admission, computed tomography and magnetic resonance imaging demonstrated a cystic mass in the pleural cavity. We resected the cyst and the adjacent lung. Histopathological examination revealed an esophageal duplication cyst. Her presenting symptoms of fever and cough may have been related to infection of the cyst.

Acute appendicitis caused by amebiasis

Abstract: We report a case of appendicitis caused by amebiasis in a 45-year-old Japanese man. He presented to our hospital with bloody stools in June 1998. Sigmoidoscopy disclosed erosion, and a biopsy of the erosion showed colitis caused by Entamoeba histolytica infection. Four months later, he was admitted to our hospital with a small elastic mass and severe pain in the lower quadrant of the abdomen, which was diagnosed as acute appendicitis. He underwent appendectomy. Histopathological examination revealed numerous E. histolytica trophozoites, and we diagnosed acute appendicitis caused by E. histolytica. The patient has been free of symptoms, colonoscopy has revealed no erosion, and biopsy has revealed no E. histolytica for 12 months after the operation.

Successfully resected hepatoblastoma in a young adult with chronic hepatitis B : report of a case

Hepatoblastoma usually occurs in children, but a few cases have also been reported in adults. We report the unusual case of hepatoblastoma in an 18-year-old adult with chronic hepatitis B. He visited a local hospital with right upper abdominal pain. Abdominal ultrasound showed a large mass in the right lobe of his liver. He was referred to our hospital and admitted for further examination. At admission, liver function tests gave slightly elevated results (aspartate aminotransferase (AST) 103 IU/l, alanine aminotransferase (ALT) 63 IU/l). A test for hepatitis virus revealed that he was a hepatitis B surface antigen (HBsAg) carrier and had experienced seroconversion. His alpha-fetoprotein (AFP) was elevated to 1 548 000 IU/ml. Abdominal ultrasound showed a 109 x 96 x 80-mm mass with mosaic pattern in the right lobe of the liver and right portal vein thrombus. Abdominal computed tomography (CT) demonstrated a large low-density mass occupying the right lobe, with some high-density parts that showed calcification. From these results, we diagnosed hepatoblastoma in a young adult. A right lobectomy was performed. Pathological examination showed a highly differentiated hepatoblastoma. Adjuvant chemotherapy was performed with cisplatin and pirarubicin. The patient has been well and free of recurrence for 12 months, and his AFP level remains almost normal.

Milk-based test as a preventive method for chylous ascites following pancreatic resection.

Background/Purpose: The incidence and natural history of postoperative chylous ascites are not well understood. This complication causes malnutrition and prolonged hospital stay. We investigated our institution’s experience involving chylous ascites, especially following pancreatectomy. Additionally, we designed a new intraoperative method dubbed the ‘milk test’ for preventing chylous ascites. Methods: Five cases of chylous ascites following pancreatectomy from April 2001 through March 2004 were studied retrospectively. The milk test was carried out prospectively. Such rates as positivity and incidence of ascites were examined. Results: Of 65 cases (40 pancreatoduodenectomy; 25 distal pancreatectomy), 5 (7.7%) developed chylous ascites following pancreatic resection. All cases underwent octreotide and total parenteral nutrition treatment. From April 2004 through March 2009, the milk test was used in 104 cases. Surgical procedures comprised pancreatoduodenectomy (n = 78) and distal pancreatectomy (n = 23). Of these cases, 23 (22.1%) tested positive. No significant difference in positive rates was observed between the procedures and diseases. After initiation of the milk test, chylous ascites incidence decreased from 7.7 to 2.9%. Conclusions: For chylous ascites, octreotide and total parenteral nutrition treatments are useful. However, the milk test was found to be a safe and effective method for prevention of chylous ascites following pancreatectomy.

Suture line recurrence in jejunal pouch replaced after total gastrectomy for gastric cancer

Abstract:We report a case of suture line recurrence in a jejunal pouch, diagnosed 4 months after total gastrectomy for advanced gastric cancer. The jejunal pouch was made with a linear stapler, without intraluminal irrigation being carried out before anastomosis, and was replaced in an interposition fashion. We propose that the recurrence was caused by the implantation of exfoliated cancer cells in either the intraluminal mucus or on a contaminated stapling device.